Isocoumarin derivatives inhibiting angiogenesis

Abstract

The present invention relates to novel isocoumarin derivatves inhibiting angiogenesis, a method for preparation thereof and pharmaceutical compositions comprising the said derivatives as pharmaceutically active ingredients. More particularly, the present invention relates to novel isocoumarin derivatves represented by formula (1), especially 6,8-dihydroxy-4-acetyl-isocoumarin, a method for preparing 6,8-dihydroxy-4-acetyl-isocoumarin from fungi, and pharmaceutical compositions comprising the compounds and/or 6,8-dihydroxy-4-acetyl-isocoumarin as pharmaceutically active ingredients, which would be effective for the treatment of angiogenic diseases such as cancers, rheumatoid arthritis and diabetic retinopathy.

What is claimed is:  
     
       1. A compound of formula 1: 
       Formula 1                    
       wherein, 
       R 1  is a hydrogen, alkyl or allyalkyl group; and  
       R 2  and R 3 , which are independently hydrogen or an alkyl group.  
     
     
       2. A compound of  claim 1 , which is a 6,8-dihydroxy-4-acetyl-isocoumarin derivative represented by the following formula 2:                    
     
     
       3. The composition of  claim 2 , which is isolated from Sesquicillium sp. Y70832. 
     
     
       4. A pharmaceutical composition comprising the compound of  claim 1 . 
     
     
       5. A pharmaceutical composition comprising the compound of  claim 2 . 
     
     
       6. A method of treating angiogenic diseases, comprising administering an effective amount of a compound of  claim 1 . 
     
     
       7. The method of  claim 6 , wherein said angiogenic disease is selected from the group comprising cancers, rheumatoid arthritis and diabetic retinopathy. 
     
     
       8. The method of  claim 6 , further comprising administering a member of the group consisting of doxorubicin, taxol, eptopoxide, camptothecin, 5-flourouracil, methotrexate and platinum complex compounds. 
     
     
       9. The method of  claim 8 , further comprising administering an anti-inflammatory drug.